Subsequent events	6 Months Ended
Jun. 30, 2021
Subsequent events.
Subsequent events	16. Subsequent events Collaboration and License Agreement On July 9, 2021, BicycleTx Limited (“BTx”), and Ionis entered into a collaboration and license agreement (the “Ionis Collaboration Agreement”). The parties entered into the Ionis Collaboration Agreement following the exercise on July 9, 2021 by Ionis of the Ionis Option granted by BTx to Ionis pursuant to the Evaluation and Option Agreement. Pursuant to the Ionis Collaboration Agreement, BTx granted to Ionis a worldwide exclusive license under BTx’s relevant technology to research, develop, manufacture and commercialize products incorporating Bicycle peptides directed to the protein coded by the gene TFRC1 (transferrin receptor) (“TfR1 Bicycles”) intended for the delivery of oligonucleotide compounds directed to targets selected by Ionis for diagnostic, therapeutic, prophylactic and preventative uses in humans. Each party will be responsible for optimization of such TfR1 Bicycles and other research and discovery activities related to TfR1 Bicycles, and thereafter Ionis will be responsible for all future research, development, manufacture and commercialization activities. Bicycle has retained certain rights, including the right to use TfR1 Bicycles for all non-oligonucleotide therapeutic purposes. Under the Ionis Collaboration Agreement, Ionis made an upfront payment to BTx of $31.0 million and an equity investment in the Company of $11.0 million. On a collaboration target-by-collaboration target basis, Ionis will be required to make a payment to BTx of a low-single-digit million dollar amount upon acceptance of an investigational new drug application for the first product directed to such collaboration target (provided that Ionis will have a credit of a high single-digit million dollar amount to be applied towards the IND acceptance fee for four collaboration targets), and Ionis will be required to make milestone payments to BTx upon the achievement of specified development and regulatory milestones of up to a low double-digit million dollar amount per collaboration target. In addition, BTx is also eligible to receive up to a low double-digit million dollar amount in cumulative sales milestone payments. BTx is entitled to receive tiered royalty payments on net sales at percentages in the low single digits, subject to certain standard reductions and offsets. Royalties will be payable, on a product-by-product and country-by-country basis, until the latest of the expiration of specified licensed patents covering such product in such country, ten years from first commercial sale of such product in such country, or expiration of marketing exclusivity for such product in such country. Either party may terminate the Ionis Collaboration Agreement for the uncured material breach of the other party or in the case of insolvency. Ionis may terminate the Ionis Collaboration Agreement for convenience on specified notice periods depending on the development stage of the applicable target, either in its entirety or on a target-by-target basis. Share Purchase Agreement Concurrently with the execution of the Ionis Collaboration Agreement on July 9, 2021, the Company entered into a share purchase agreement (the “Share Purchase Agreement”) with Ionis, pursuant to which Ionis purchased 282,485 of the Company’s ordinary shares (the “Shares”) at a price per Share of $38.94, for an aggregate purchase price of approximately $11.0 million. Pursuant to the terms of the Share Purchase Agreement, Ionis has agreed not to, without the Company’s prior written consent and subject to certain conditions and exceptions, among other things, directly or indirectly acquire additional shares of the Company’s outstanding equity securities, seek or propose a tender or exchange offer, merger or other business combination involving the Company, solicit proxies or consents with respect to any matter, or undertake other specified actions related to the potential acquisition of additional equity interests in the Company (collectively, the “Standstill Restrictions”). The Standstill Restrictions will expire on the 18-month anniversary of the Share Purchase Agreement. The Share Purchase Agreement also provides that, subject to limited exceptions, Ionis will hold and not sell any of the Shares until the earlier of (i) the first anniversary of the closing of the sale of the Shares under the Share Purchase Agreement (the “Closing Date”) and (ii) the termination of the Ionis Collaboration Agreement pursuant to its terms (provided, however, that in the event the termination of the Ionis Collaboration Agreement occurs less than six months after the Closing Date, Ionis shall hold and will not sell or otherwise enter into a transaction regarding the Shares until at least the date that is six months after the Closing Date). ATM Sales Previously, on October 2, 2020, the Company entered into a Sales Agreement with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc. with respect to an ATM program under which the Company may offer and sell, from time to time at its sole discretion, ADSs through the Sales Agents, representing the same number of ordinary shares. As of June 30, 2021, the Company had registered the sale of up to $225.0 million of ADSs, of which $125.0 million had been sold pursuant to the Sales Agreement as of June 30, 2020. In July 2021, the Company issued and sold 930,900 ADSs, representing the same number of ordinary shares, pursuant to its ATM program for gross proceeds of $30.8 million, resulting in net proceeds of $29.9 million, after deducting sales commissions and offering expenses.

Subsequent events

6 Months Ended

Jun. 30, 2021

16. Subsequent events

Collaboration and License Agreement

On July 9, 2021, BicycleTx Limited (“BTx”), and Ionis entered into a collaboration and license agreement (the “Ionis Collaboration Agreement”). The parties entered into the Ionis Collaboration Agreement following the exercise on July 9, 2021 by Ionis of the Ionis Option granted by BTx to Ionis pursuant to the Evaluation and Option Agreement. Pursuant to the Ionis Collaboration Agreement, BTx granted to Ionis a worldwide exclusive license under BTx’s relevant technology to research, develop, manufacture and commercialize products incorporating Bicycle peptides directed to the protein coded by the gene TFRC1 (transferrin receptor) (“TfR1 Bicycles”) intended for the delivery of oligonucleotide compounds directed to targets selected by Ionis for diagnostic, therapeutic, prophylactic and preventative uses in humans. Each party will be responsible for optimization of such TfR1 Bicycles and other research and discovery activities related to TfR1 Bicycles, and thereafter Ionis will be responsible for all future research, development, manufacture and commercialization activities. Bicycle has retained certain rights, including the right to use TfR1 Bicycles for all non-oligonucleotide therapeutic purposes.

Under the Ionis Collaboration Agreement, Ionis made an upfront payment to BTx of $31.0 million and an equity investment in the Company of $11.0 million. On a collaboration target-by-collaboration target basis, Ionis will be required to make a payment to BTx of a low-single-digit million dollar amount upon acceptance of an investigational new drug application for the first product directed to such collaboration target (provided that Ionis will have a credit of a high single-digit million dollar amount to be applied towards the IND acceptance fee for four collaboration targets), and Ionis will be required to make milestone payments to BTx upon the achievement of specified development and regulatory milestones of up to a low double-digit million dollar amount per collaboration target. In addition, BTx is also eligible to receive up to a low double-digit million dollar amount in cumulative sales milestone payments. BTx is entitled to receive tiered royalty payments on net sales at percentages in the low single digits, subject to certain standard reductions and offsets. Royalties will be payable, on a product-by-product and country-by-country basis, until the latest of the expiration of specified licensed patents covering such product in such country, ten years from first commercial sale of such product in such country, or expiration of marketing exclusivity for such product in such country.

Either party may terminate the Ionis Collaboration Agreement for the uncured material breach of the other party or in the case of insolvency. Ionis may terminate the Ionis Collaboration Agreement for convenience on specified notice periods depending on the development stage of the applicable target, either in its entirety or on a target-by-target basis.

Share Purchase Agreement

Concurrently with the execution of the Ionis Collaboration Agreement on July 9, 2021, the Company entered into a share purchase agreement (the “Share Purchase Agreement”) with Ionis, pursuant to which Ionis purchased 282,485 of the Company’s ordinary shares (the “Shares”) at a price per Share of $38.94, for an aggregate purchase price of approximately $11.0 million.

Pursuant to the terms of the Share Purchase Agreement, Ionis has agreed not to, without the Company’s prior written consent and subject to certain conditions and exceptions, among other things, directly or indirectly acquire additional shares of the Company’s outstanding equity securities, seek or propose a tender or exchange offer, merger or other business combination involving the Company, solicit proxies or consents with respect to any matter, or undertake other specified actions related to the potential acquisition of additional equity interests in the Company (collectively, the “Standstill Restrictions”). The Standstill Restrictions will expire on the 18-month anniversary of the Share Purchase Agreement.

The Share Purchase Agreement also provides that, subject to limited exceptions, Ionis will hold and not sell any of the Shares until the earlier of (i) the first anniversary of the closing of the sale of the Shares under the Share Purchase Agreement (the “Closing Date”) and (ii) the termination of the Ionis Collaboration Agreement pursuant to its terms (provided, however, that in the event the termination of the Ionis Collaboration Agreement occurs less than six months after the Closing Date, Ionis shall hold and will not sell or otherwise enter into a transaction regarding the Shares until at least the date that is six months after the Closing Date).

ATM Sales

Previously, on October 2, 2020, the Company entered into a Sales Agreement with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc. with respect to an ATM program under which the Company may offer and sell, from time to time at its sole discretion, ADSs through the Sales Agents, representing the same number of ordinary shares. As of June 30, 2021, the Company had registered the sale of up to $225.0 million of ADSs, of which $125.0 million had been sold pursuant to the Sales Agreement as of June 30, 2020. In July 2021, the Company issued and sold 930,900 ADSs, representing the same number of ordinary shares, pursuant to its ATM program for gross proceeds of $30.8 million, resulting in net proceeds of $29.9 million, after deducting sales commissions and offering expenses.